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人类心脏的发育转录组。

The developmental transcriptome of the human heart.

机构信息

School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.

Department of Psychology, Durham University, Durham, DH1 3LE, UK.

出版信息

Sci Rep. 2018 Oct 18;8(1):15362. doi: 10.1038/s41598-018-33837-6.

DOI:10.1038/s41598-018-33837-6
PMID:30337648
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6194117/
Abstract

The human heart develops through complex mechanisms producing morphological and functional changes during gestation. We have recently demonstrated using diffusion tensor MRI that over the relatively short space of 40 days, between 100-140 days gestational age, the ventricular myocardium transforms from a disorganised tissue to the ordered structure characteristic of mature cardiac tissue. However, the genetic basis underpinning this maturation is unclear. Herein, we have used RNA-Seq to establish the developmentally-regulated transcriptome of gene expression in the developing human heart across three gestational ages in the first and second trimester. By comparing 9 weeks gestational age (WGA) with 12 WGA, we find 288 genes show significant differential expression. 305 genes were significantly altered comparing 12 and 16 WGA, and 806 genes differentially expressed between 9 and 16 WGA. Network analysis was used to identify genetic interactions, node properties and gene ontology categories. In summary, we present a comprehensive transcriptomic analysis of human heart development during early gestation, and identify differentially expressed genes during heart development between 9 and 16 weeks, overlapping the first and early second trimester.

摘要

人类心脏通过复杂的机制发育,在妊娠期会发生形态和功能上的变化。我们最近使用扩散张量 MRI 证明,在相对较短的 40 天内,即 100-140 天的妊娠期内,心室心肌从无序组织转变为成熟心脏组织特有的有序结构。然而,支持这种成熟的遗传基础尚不清楚。在此,我们使用 RNA-Seq 技术在妊娠早期和中期的三个妊娠龄阶段,建立了人类心脏发育过程中基因表达的发育调控转录组。通过比较 9 周龄(WGA)与 12 周龄,我们发现 288 个基因的表达存在显著差异。比较 12 周龄和 16 周龄,有 305 个基因发生显著变化,而在 9 周龄和 16 周龄之间有 806 个基因表达差异。网络分析用于识别遗传相互作用、节点特性和基因本体类别。总之,我们对妊娠早期人类心脏发育进行了全面的转录组分析,并确定了在 9 至 16 周心脏发育过程中差异表达的基因,这些基因与妊娠早期和早期中期重叠。

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Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy.
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